P1100: PET INTERIM RESULTS COULD PROMPTLY SELECT FOLLICULAR LYMPHOMA PATIENTS IN NEED OF MAINTENANCE THERAPY. POTENTIAL ADDITIONAL VALUE OF CFDNA.
Authors: Maria Poza, Patricia López-Pereira, Gloria Figaredo García-Mina, Irene Zamanillo Herreros, Rodrigo Íñiguez García, Sandra Gómez-Rojas, Gloria Pérez Segura, Rosa Ayala, Tycho Baumann, Antonia Rodriguez Izquierdo, Santiago Barrio García, Alejandro Martín-Muñoz, Pilar Sarandeses, Enrique Revilla, Sara Dorado, Margarita Rodriguez, Joaquín Martínez-López, Ana Isabel Jimenez Ubieto
Journal: HemaSphere (2023)

Topic: 18. Indolent and mantle-cell non-Hodgkin lymphoma - Clinical Background: Follicular Lymphoma (FL) patients frequently achieve long remissions with frontline chemoimmunotherapy (CIT); nevertheless, a subset of patients will experience early progression, which is associated with poor subsequent outcomes. Fluoro-[18F]-deoxy-2-D-glucose positron emission tomography (PET/CT) and more recently liqBio-MRD performed at the end of CIT induction can identify patients at significantly higher risk of relapse. Aims: The aim of this study is to analyze if an interim PET/TC scan could earlier identify high-risk FL. Methods: We retrospectively identified 121 patients with grade 1–3A FL who had end of treatment (EOT) and interim PET/CT (after 4 cycles of frontline CIT) at 3 academic centers between 2012-2022. PET/CT were analyzed using Deauville score (DS). A positive result on the PET/CT was determined by a DS of four or five, while scores one to three were considered negative. Interim cell free DNA (cfDNA) was available in 15 patients, so we could measure MRD by NGS, as previously described (Jiménez-Ubieto 2023). Results: Most patients were treated with R‐CHOP (n= 94; 78%) or rituximab-bendamustine (n= 24; 20%). Rituximab maintenance (RM) after induction was used in 87%. The median follow-up for all patients was 34 months (3-115). During follow-up period, 34 patients (28%) relapsed, 21 (17,5%) within 24 months after CIT, and 12 patients died. Histological transformation (HT) rate was 2.5%. The interim and EOT CR rate was 66% and 81.5%, respectively. On iPET/CT, 41 (34%) patients were PET/CT(+), 3 were classified as refractory disease and were excluded from progression-free survival analysis. The estimated PFS at 5 years was 72% in patients with a negative iPET/CT versus 29% in those with a positive iPET/CT(p < 0.001). 34% and 7.6% of patients with iPET/CT(+) and (-) presented POD24, respectively, (p<0.001; HR 7,89). iPET/CT(-) presented a negative predictive value of 94% for POD24 (Figure 1a).). Interestingly, patients who had a positive iPET/CT and eventually converted to a negative PET (n = 9) had inferior PFS than those for whom both examinations were negative (n = 95; 2-year PFS, 71.5% v 93.9%, p = 0.004). PET/CTEOT findings were also predictive of relapse, with 2-years PFS 47% in PET/CTEOT(+) vs 89% in PET/CTEOT(-) (p<.001). Additionally, in 78 patients with iPET/CT(-) and 93 patients with PET/CTEOT(-) MR was not relevant to predict POD24 (2-year PFS of 93.5%/85.7% and 91.3%/87.5%, respectively). Notwithstanding, patients with iPET/CT(+) or EOTPET/CT(+) MR had a clear impact in predicting POD24 (p<0.05). Additionally, SUVmax>3,7 in the iPET/CT was predictive for HT, regardless of being iPET/CT(-). In 15 patients with interim cfDNA MRD analysis (after 4 cycles); our test was able to found trackable mutations in 14 patients (93%). 4/14 patients relapsed after a median of 8.5 months. 3/4 of the relapsing patients had a MRD interim(+) and all the non-relapsing patients a negative MRD test (p<.001). Interestingly, of the 10 non-relapsing patients (all MRD neg) 2 have iPET/CT(+) (mesenteric masses). A biopsy excluded lymphoma; confirming the false positive value of the PET/CT. Summary/Conclusion: Response assessment by PET/CT at mid-induction can identify FL patients at high risk of failure early on during first line ICT and is able promptly select patients in whom maintenance therapy could be avoided. Clinical trial focus on decreasing treatment shoud be investigated in iPET/CT(-) patients. Additionally, LiqBIO-MRD is a promising technique complementary to PET/TC able to identify the non-depreciable rates of false positive PET/CT scans.Keywords: Follicular lymphoma, Progression, FDG-PET, Maintenance